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Identification of a shared genetic risk locus for Kawasaki disease and immunoglobulin A vasculitis by a cross-phenotype meta-analysis

Abstract: Objectives: Combining of genomic data of different pathologies as a single phenotype has emerged as a useful strategy to identify genetic risk loci shared among immune-mediated diseases. Our study aimed to increase our knowledge of the genetic contribution to Kawasaki disease (KD) and IgA vasculitis (IgAV) by performing the first comprehensive large-scale analysis on the genetic overlap between them. Methods: A total of 1190 vasculitis patients and 11 302 healthy controls were analysed. First, in the discovery phase, genome-wide data of 405 KD patients and 6252 controls and 215 IgAV patients and 1324 controls, all of European origin, were combined using an inverse variance meta-analysis. Second, the top associated polymorphisms were selected for replication in additional independent cohorts (570 cases and 3726 controls). Polymorphisms with P-values ?5 × 10-8 in the global IgAV-KD meta-analysis were considered as shared genetic risk loci. Results: A genetic variant, rs3743841, located in an intron of the NAGPA gene, reached genome-wide significance in the cross-disease meta-analysis (P = 8.06 × 10-10). Additionally, when IgAV was individually analysed, a strong association between rs3743841 and this vasculitis was also evident [P = 1.25 × 10-7; odds ratio = 1.47 (95% CI 1.27, 1.69)]. In silico functional annotation showed that this polymorphism acts as a regulatory variant modulating the expression levels of the NAGPA and SEC14L5 genes. Conclusion: We identified a new risk locus with pleiotropic effects on the two childhood vasculitides analysed. This locus represents the strongest non-HLA signal described for IgAV to date.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: Rheumatology (Oxford) . 2022 Mar 2;61(3):1204-1210

Editorial: Oxford University Press

 Año de publicación: 2022

Nº de páginas: 15

Tipo de publicación: Artículo de Revista

 DOI: 10.1093/rheumatology/keab443

ISSN: 1462-0324,1462-0332

Url de la publicación: https://www.doi.org/10.1093/rheumatology/keab443

Autoría

CARMONA, ELIO G

GARCÍA-GIMÉNEZ, JOSE A

LÓPEZ-MEJÍAS, RAQUEL

KHOR, CHIEA CHUEN

LEE, JONG-KEUK

TASKIRAN, EKIM

OZEN, SEZA

HOCEVAR, ALOJZIJA

LIU, LILI

GORENJAK, MARIO

POTOCNIK, UROŠ

KIRYLUK, KRZYSZTOF

ORTEGO-CENTENO, NORBERTO

CID, MARÍA C

HERNÁNDEZ-RODRÍGUEZ, JOSÉ

CASTAÑEDA, SANTOS

MARTÍN, JAVIER

MÁRQUEZ, ANA